Sudden death and myocardial infarction in first degree relatives as predictors of primary cardiac arrest

The hypothesis that family history (FH) of myocardial infarction (MI) and FH of sudden death (SD) are both independent risk factors for primary cardiac arrest (PCA) was examined in a case-control study. PCA cases were attended by paramedics (1988-1994) and community-based age and sex matched controls were identified. Subjects (25-74 years) were free of prior clinically-recognized heart disease and major co-morbidity. Interviewers obtained a detailed history of MI and SD in first-degree relatives from spouses of 235 cases and 374 control subjects. A parental history of early-onset SD (age <65) was associated with an increased risk of PCA (odds ratio (OR)=2.69, 95% CI=1.35-5.36), after adjustment for parental history of MI and other risk factors. A parental history of late-onset SD was not associated with PCA risk (OR=0.94, 95% CI=0.55-1.62). Additionally, parental history of SD was related to early-onset PCA (OR=1.89, 95% CI=1.08-3.30) but not to late-onset PCA (OR=0.89, 95% CI=0.49-1.61). In contrast, parental MI (early/late) was related to PCA (early/late), after adjustment for other risk factors and parental history of SD. Similar results were observed in first-degree relatives. Findings suggest a potential role of familial factors related to both MI and SD in PCA. Stronger findings for a familial patterning of PCA were noted for early onset disease in cases and their relatives.     

Role of DNA-Dependent RNA Polymerase III in the Transcription of the tRNA and 5S RNA Genes

Mouse myeloma cells have previously been shown (L. B. Schwartz, V. E. F. Sklar, J. A. Jaehning, R. Weinmann & R. G. Roeder, submitted for publication) to contain two chromatographically distinct forms of RNA polymerase III (designated III(A) and III(B)). The enzymes are unaffected by low alpha-amanitin concentrations which completely inhibit RNA polymerase II, but they exhibit characteristic inhibition curves (identical for III(A) and III(B)) at higher toxin concentrations. RNA polymerase I was unaffected at all alpha-amanitin concentrations tested. Myeloma RNA polymerases II, III(A), and III(B) appear to be inhibited by the same mechanism, since the toxin rapidly blocks chain elongation by each enzyme. The characteristic alpha-amanitin sensitivity of RNA polymerase III has been employed in studies of the function(s) of the class III RNA polymerases.Isolated myeloma nuclei and nucleoli contińue to synthesize RNA via the endogenous RNA polymerases when incubated in vitro. With nuclei, newly synthesized 4S precursor (pre-4S) and 5S RNA species were detected by electrophoretic analysis either of the total nuclear RNA or of the RNA released into the supernatant during incubation. The synthesis of both pre-4S and 5S RNA species was inhibited by alpha-amanitin, but only at high concentrations; and the alpha-amanitin inhibition curves for these RNAs were identical to those obtained for solubilized RNA polymerases III(A) and III(B). In control experiments it was shown that the endogenous RNA polymerase II activity of isolated nuclei was inhibited by alpha-amanitin concentrations similar to those required to inhibit purified enzyme II. However, 40-50% of the endogenous activity of nuclei and 100% of the endogenous activity of purified nucleoli was completely resistant to the high alpha-amanitin concentrations necessary to inhibit the RNA polymerase III activities. These experiments rule out nonspecific inhibitory effects in the endogenous systems.These results unequivocally demonstrate the role of RNA polymerase III (III(A) and/or III(B)) in the synthesis of (pre) 4S RNAs and a 5S RNA species.     

Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile

Cancer Causes & Control - The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal...